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Biomedical subjects

S J Hunt

Publications and source records attributed to S J Hunt.

At least 19 recordsLinked to original sources

A case of childhood sarcoidosis.

Cutaneous sarcoidosis is rare in children. We report a case of a 5-year-old Bangladeshi girl who presented with fever, a papular eruption on the lower limbs and trunk, malaise, anorexia and weight loss. There was multisystem involvement with marked hepatosplenomegaly, generalized lymphadenopathy, parotid fullness and chronic uveitis. Pulmonary infiltrates were seen on the chest X-ray. Histology of a skin biopsy showed naked noncaseating granulomata and PCR for Mycobacterium tuberculosis was negative. A clinical diagnosis of sarcoidosis was made. The patient was treated with oral prednisolone (2 mg/kg per day). An excellent clinical response with resolution of the rash and improvement of extracutaneous signs was noted within 3 months and she remains well on low-dose prednisolone on alternate days. We discuss the presentation and management of sarcoidosis in children, and highlight the potential difficulty in differentiating this from disseminated tuberculosis.

Anti-Inflammatory Agents↗

Pharmacological profile of ZD1611, a novel, orally active endothelin ETA receptor antagonist.

The endothelins (ETs), potent vasoconstrictor peptides, have been implicated in the pathogenesis of various cardiovascular disorders. In the present study, we describe the novel, potent, orally active, selective ET(A) receptor antagonist ZD1611 [3-(4-[3-(3-methoxy-5-methylpyrazin-2-ylsulfamoyl)-2-pyridyl ]phenyl)- 2,2-dimethylpropanoic acid]. ZD1611 competitively inhibited (125)I-labeled ET-1 binding at human cloned ET(A) and ET(B) receptors with pIC(50) values of 8.6 +/- 0.1 and 5.6 +/- 0.1, respectively, showing 1000-fold selectivity for the ET(A) receptor. ZD1611 caused a parallel rightward shift of the concentration response curve to ET-1 in the rat isolated aorta yielding a concentration of antagonist that caused a 2-fold rightward shift in the ET-1-response curve (pA(2)) of 7.5 +/- 0.3. When administered i. v. to anesthetized rats and dogs, ZD1611 caused dose-related rightward shifts of partial dose-response curves to the precursor of ET-1, big ET-1. Threshold doses for significant antagonist activity were determined as 0.1 mg/kg and 0.3 mg/kg in the rat and dog, respectively. Importantly, ZD1611 was able to reverse an established big ET-1-induced pressor response in pithed rats in the presence of continuous big ET-1 infusion. Failure of ZD1611 to inhibit the BQ3020 (ET(B)-selective)-induced depressor response in pithed rats indicated a lack of activity at the endothelial ET(B) receptor. ZD1611 was orally active in the rat at 0.3 mg/kg and had a duration of action of more than 7 h, and, in the dog, a dose of 0.6 mg/kg p.o. was active for at least 6 h. In conclusion, these data demonstrate that ZD1611 is a potent and orally active, selective ET(A) receptor antagonist with a long duration of action which may be of therapeutic use.

Administration, Oral↗

New non-peptide endothelin-A receptor antagonists: synthesis, biological properties, and structure-activity relationships of 5-(dimethylamino)-N-pyridyl-,-N-pyrimidinyl-,-N-pyridazinyl-, and -N-pyrazinyl-1-naphthalenesulfonamides.

Use of automated synthesis led to the discovery of several 6-membered nitrogen heterocycles as replacements for the N-isoxazolyl substituent present in the 1-naphthalenesulfonamides endothelin-A (ETA) antagonist 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesu lfo namides (BMS 182874). In each of these heterocycles, a small substituent such as halogen para to the position of attachment to the sulfonamide nitrogen atom was found to be advantageous for ETA receptor affinity. Of these heterocycles, 2-pyrazines offered the greatest scope for improving receptor affinity. Optimization of the substituents at the 3- and 5-positions in the pyrazine ring led to potent, ETA-selective compounds such as 5-(dimethylamino)-N-(5-chloro-3-methoxy-2-pyrazinyl)-1- naphthalenesulfonamides (7m, ETA pIC50 8.1). When dosed orally at 10 mg/kg to conscious, normotensive rats infused with big ET-1, compounds such as 7m showed significant inhibition of the pressor response with a duration of effect lasting for the 5-h course of the experiment.

Animals↗

Assessing bedside cardiologic examination skills using "Harvey," a cardiology patient simulator.

OBJECTIVE: To assess the cardiovascular physical examination skills of emergency medicine (EM) housestaff and attending physicians. METHODS: Prospective, cohort assessment of EM housestaff and faculty performance on 3 valvular abnormality simulations (mitral regurgitation, mitral stenosis, and aortic regurgitation) conducted on the cardiology patient simulator, "Harvey." Participants examined each of the 3 study disease simulations and proposed a diagnosis (session I). They were then given a cardiac examination form and repeated the programmed simulations (session II). The examination form was used to prompt physicians to interpret 23 separate cardiac findings for each simulation in a multiple-choice format. RESULTS: Forty-six EM housestaff (PGY1-3) and attending physicians were tested over a 2-month study period. Physician responses did not differ significantly among the different levels of postgraduate training. The overall correct response rates for participants were 59% for aortic regurgitation, 48% for mitral regurgitation, and 17% for mitral stenosis. For aortic regurgitation, recognition of a widened pulse pressure and recognition of diastolic decrescendo murmur were associated with a correct diagnosis (p < 0.01). For mitral regurgitation, correct assessment of the contour of the holosystolic murmur predicted a correct diagnosis (p < 0.001). For mitral stenosis, proper characterization of the mitral area diastolic murmur predicted a correct diagnosis (p < 0.001). CONCLUSION: Housestaff and faculty had difficulty establishing a correct diagnosis for simulations of 3 common valvular heart diseases. However, accurate recognition of a few critical signs was associated with a correct diagnosis in each simulation. Training programs may need to focus attention on selected key components of the cardiovascular examination to facilitate teaching of physical diagnosis.

Clinical Competence↗

Cutaneous T-cell lymphoma of the eyelid in a patient with acquired immunodeficiency syndrome.

Cutaneous T-cell lymphoma (CTCL) is significantly less common than B-cell lymphoma in patients with acquired immunodeficiency syndrome (AIDS). Periocular involvement by CTCL usually occurs in the setting of more widespread plaque or tumor-stage disease; therefore, CTCL localized solely to the periocular region is rare. We report the case of a 38-year-old Hispanic woman with AIDS and an enlarging tumor of the left upper eyelid. The clinical differential diagnosis included various infections and neoplasms. Examination of an incisional biopsy specimen revealed a dense infiltrate of atypical lymphocytes that labeled as T cells with use of the immunoperoxidase technique. The tumor subsequently regressed with local radiotherapy. Eyelid CTCL is reviewed and the differential diagnosis of eyelid lesions is reviewed.

AIDS-Related Opportunistic Infections↗

Cutaneous necrosis and multinucleate epidermal cells associated with intravenous phenytoin.

A 23-year-old white man experienced burning pain up his right forearm while receiving phenytoin intravenously in the dorsal wrist. Swelling occurred, followed a few days later by an erythematous eruption that eventuated in superficial skin sloughing. The histopathology of two right forearm biopsies, taken a few days apart 3 to 4 weeks after the infusion, was characterized by partial epidermal necrosis and frequent multinucleate keratinocytes. Localized cutaneous reactions to phenytoin and the occurrence of multinucleate epidermal cells in inflammatory skin disease are reviewed.

Adult↗

Solitary reticulohistiocytoma in pregnancy: immunohistochemical and ultrastructural study of a case with unusual immunophenotype.

A case of a solitary reticulohistiocytoma during pregnancy is reported. The tumor arose on the right thigh of a 31-year-old woman during the 2nd month of gestation. Physical examination 6 months later revealed a 9 x 6 mm yellowish white papule. A biopsy showed a dermal proliferation of spindle to polygonal cells embedded in fibrous tissue with admixed neutrophils, eosinophils, and lymphocytes. Immunohistochemistry was positive for S-100, factor XIIIa, HLA-DR, KP-1, vimentin, and neuron-specific enolase. Ultrastructurally, the cells showed abundant lipid, lysozomes, and endoplasmic reticulum. No Birbeck granules could be identified. The results suggest an aberrant immunophenotype intermediate between indeterminate cells and dermal dendritic cells. The relationship of these lineages to reticulohistiocytoma and other dermal proliferative disorders is reviewed.

Adult↗

Sebaceous adenoma with a cutaneous horn.

Cutaneous horns are common lesions that usually represent actinic keratoses, verrucae, seborrheic keratoses, and squamous cell carcinomas. We present a remarkable example of a sebaceous adenoma with cutaneous horn formation. The solitary lesion occurred over the left clavicle of a 71-year-old man without evidence of the Muir-Torre syndrome. There have been only three previous reports of sebaceous tumors (one sebaceous adenoma and two sebaceous carcinomas) producing cutaneous horns, the latter of which are actually pseudohorns, exophytic extensions of tumor without hyperkeratosis.

Adenoma↗

Cutaneous Acanthamoeba infection in the acquired immunodeficiency syndrome: response to multidrug therapy.

Acanthamoeba, a free-living ameba of soil and water, produces the rare infections of granulomatous amebic encephalitis and amebic keratitis. We report a 38-year-old white man with the acquired immunodeficiency syndrome (AIDS) who experienced Acanthamoeba infection that presented as multiple skin nodules without associated encephalitis. Histologic examination revealed necrotizing granulomatous inflammation with numerous amebic organisms that were cultured and identified as Acanthamoeba group 2, probably Acanthamoeba castellani by monoclonal antibodies. Results of in vitro susceptibility testing demonstrated resistance to all six tested drugs. A partial clinical response, however, was obtained with multidrug therapy.

AIDS-Related Opportunistic Infections↗

Cutaneous T-cell lymphoma: utility of antibodies to the variable regions of the human T-cell antigen receptor.

BACKGROUND: The clonotypic 90 kd Ti heterodimer of the human T-cell antigen receptor is composed of two distinct chains (alpha beta or rarely tau delta) that result from the recombination of variable (V), constant, joining, and, in the case of beta chains, additional diversity regions. OBJECTIVE: The variable region expression of human cutaneous T-cell lymphoma (CTCL) was studied. METHODS: Biopsy specimens from 13 patients with CTCL (7 plaque, 3 tumor stage, 3 Sézary syndrome) were examined immunohistochemically by a panel of seven commercially available monoclonal V-region antibodies. RESULTS: Two patients had significant anti-V-region staining. One patient with Sézary syndrome had two lesions, subjected to biopsy 4 months apart, that reacted with beta V5(a), a specificity previously documented by flow cytometry of leukemic cells. A patient with plaque-stage CTCL, negative for T-cell gene rearrangement by Southern blot, demonstrated reactivity with beta V5(c) largely limited to epidermotropic lymphocytes. CONCLUSION: Panels of V-region antibodies should be useful reagents for diagnosis and follow-up of CTCL.

Adult↗

Primary cutaneous fungal infection after solid-organ transplantation: report of five cases and review.

Solid-organ transplant recipients who are receiving immunosuppressive therapy are at increased risk of acquiring opportunistic infections, particularly fungal infections. We present the cases of five liver transplant recipients who developed primary cutaneous opportunistic fungal infections that remained localized to the skin. These cases are compared with 27 previously reported cases of primary cutaneous fungal infections. In these previously reported cases, administration of systemic antifungal medications, including amphotericin B, ketoconazole, griseofulvin, and miconazole, resulted in a 71% survival rate. Medical and surgical therapy together resulted in an 86% survival rate, and surgical excision resulted in a 100% survival rate. Thus, regardless of the age of the patient, type of immunosuppressive therapy, clinical presentation, or organisms involved, surgical excision yielded the highest cure rate. When possible, surgical excision should be performed on solid-organ transplant recipients who acquire opportunistic fungal infections.

Adult↗

Primary cutaneous aspergillosis near central venous catheters in patients with the acquired immunodeficiency syndrome.

BACKGROUND: Aspergillosis in patients with the acquired immunodeficiency syndrome is unusual, and the clinicopathologic features of primary cutaneous aspergillosis in this setting are undefined. Our findings show that the manifestations can differ from those of primary cutaneous aspergillosis in other immunocompromised patients. OBSERVATIONS: Two men with the acquired immunodeficiency syndrome developed foci of primary cutaneous aspergillosis beneath adhesive tape near central venous catheter sites. Typical lesions were flesh-colored to pink, umbilicated papules that clinically resembled molluscum contagiosum. Biopsy specimens showed variably ruptured follicles that contained collections of fungal hyphae typical of Aspergillus species. Cultures in one case identified Aspergillus fumigatus. The use of nonocclusive dressings and local wound care resulted in involution of several lesions. CONCLUSIONS: Primary cutaneous aspergillosis begins as saprophytic involvement of hair follicles secondary to the altered microenvironment beneath adhesive tape. Systemic antifungal therapy is prudent, but in the absence of neutropenia or other traditional risk factors for dissemination, it appears that Aspergillus in patients with the acquired immunodeficiency syndrome can produce relatively indolent cutaneous lesions with a tendency to resolve once precipitating factors are removed.

Acquired Immunodeficiency Syndrome↗

Acquired benign and "borderline" vascular lesions.

In recent years, the classification of vascular lesions has been expanded and modified with the addition of several newly described entities, the redefinition of others, the recognition of lesions of borderline biologic behavior, and the need to avoid misdiagnosis with early Kaposi's sarcoma. This review clarifies the nomenclature, updates information on previously known lesions, and summarizes data on several recently discovered, lesser-known entities such as glomeruloid hemangioma, microvenular hemangioma, and multinucleate cell angiohistiocytoma. Clinicopathologic features and differential diagnosis are emphasized.

Angiokeratoma↗